Abstract
The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crystallography. The three peptide/MHC ligands include weak agonists and antagonists with different affinities for TCR. The three-dimensional structures of the three A6-TCR/peptide/HLA-A2 complexes are remarkably similar to each other and to the wild-type agonist complex, with minor adjustments at the interface to accommodate the peptide substitutions (P6A, V7R, and Y8A). The lack of correlation between structural changes and the type of T cell signals induced provides direct evidence that different signals are not generated by different ligand-induced conformational changes in the alphabeta TCR.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Substitution / immunology
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Gene Products, tax / biosynthesis
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Gene Products, tax / chemistry
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Gene Products, tax / immunology
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HLA-A2 Antigen / biosynthesis
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HLA-A2 Antigen / chemistry*
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HLA-A2 Antigen / physiology
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Humans
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Kinetics
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Macromolecular Substances
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Major Histocompatibility Complex / physiology
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Peptides / agonists
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Peptides / antagonists & inhibitors
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Peptides / chemistry*
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Peptides / immunology
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Receptors, Antigen, T-Cell, alpha-beta / agonists
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Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors
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Receptors, Antigen, T-Cell, alpha-beta / chemistry*
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Receptors, Antigen, T-Cell, alpha-beta / physiology
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Signal Transduction / immunology*
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Surface Properties
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T-Lymphocytes / chemistry
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
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Thermodynamics
Substances
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Gene Products, tax
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HLA-A2 Antigen
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Macromolecular Substances
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Peptides
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Receptors, Antigen, T-Cell, alpha-beta